This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The CTS is responsible for synchronizing an organism to the external 24-hour day (referred to as entrainment) as well as providing internal synchronization between an organism's physiological systems. Problems seen when living under non-24 hour schedules can include decreased performance, jet-lag, and physical dysfunctions associated with shift work. In addition, circadian dysfunction has a high comorbidity with some sleep and mental disorders, e.g. both endogenous and winter depression. Sleep deficits, from whatever cause, are responsible for a number of physiological and behavioral problems including attention and performance deficits and have been linked with metabolic syndrome and other pathologies. The mechanism for generation of the daily circadian rhythm in the suprachiasmatic nucleus, the 'master clock'involves several negative feedback loops of expressed proteins affecting their own gene expression. Inhibition of a kinase, which is responsible for phosphorylation of a key clock protein PER, extends the timing of this feedback loop, effectively phase delaying the clock. These studies will determine the effects of a kinase inhibitor on phase shifting the rhesus CTS and altering sleep timing and pattern. In addition to increasing our knowledge of circadian rhythms and sleep, this information could be used to design pharmacological treatments that could be used to lessen the detrimental effects of shift work or jet lag, to enhance entrainment and sleep in affected groups, for example in the elderly.